Light-triggered release from polymeric capsules is a key tool for delivering encapsulated molecules to targeted tissues with spatial and temporal control. Systems that respond to near-infrared (NIR) wavelengths (650-1300 nm) are particularly attractive due to the deep penetration depth with low attenuation, which allow low NIR irradiation to penetrate through several centimeters of tissue with minimal cytotoxicity. Use of NIR as a trigger for release of drugs from polymer nanocarriers is an active area of research, however, the approaches reported thus far experience significant drawbacks that limit their biomedical relevance.
In one common approach, gold or other metal nanostructures are incorporated into polymer capsules to generate heat upon absorption of NIR light, loosening the surrounding polymer matrix to release therapeutics. This approach is limited by the controversial biocompatibility of metal nanostructures as well as the considerable heat they generate upon NIR absorption, which may be detrimental to tissue. For example, temperature changes as high as ˜40° C. following 30 minutes of irradiation at 1.1 W, and from room temperature to boiling of aqueous solution in 5 min at 1.5 W have been reported. This excessive heating of the surroundings could potentially damage cells. This gold-assisted thermal plasticization concept is also known to be limited to heat-stable cargo, as the temperature rise around the metal particle has been shown to be well above 250° C. Over time, extensive irradiation of gold nanostructures with high power NIR light can also cause irreversible damage to the metal nanoparticles through melting, diminishing their photothermal responsiveness over time.
Alternatively, nanocarriers can also be formulated from polymers containing photo-responsive modalities that respond through chemical changes such as isomerization, oxidation, dimerization, and bond cleavage. In order to make use of the inherently low energy of NIR light, these mechanisms all require simultaneous two-photon absorption, necessitating the use of high powered and focused pulsed NIR lasers, with energies that may exceed the damage threshold of biological tissue. Recently, the limitations of two-photon photochemistry have been overcome by coupling the photosensitive polymer nanocarriers to lanthanide-doped up-converting nanoparticles (UCNPs) that sequentially absorb multiple NIR photons and convert them into higher-energy photons in the UV region. Because simultaneous absorption of excitation photons is not required, UCNPs provide for triggered release in response to biologically benign excitation power densities. However, UCNPs contain rare-earth heavy elements that may prove to be toxic in vitro and in vivo.
Although of great interest for some application, these strategies all have significant barriers to widespread application, especially for biomedical uses. Accordingly, there is a need for more biologically benign strategies to obtain remote-controlled photo-release using NIR light that would overcome these limitations.